摘要:

The effects of antidepressants and calcium (Ca2+) antagonists on serotonin (5-HT)-induced Ca2+ increase were investigated in single C6BU-1 glioma cells with digital imaging microscopy. Application of 5-HT (100 nM – 100 µM) caused a rapid and reversible rise of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner. In the absence of extracellular Ca2+, the sustained phase of the [Ca2+]i response was strongly reduced, which was greater than the suppression of the initial peak. This suggests that the peak value is mainly due to internal Ca2+ storage sites, and the sustained phase is mainly composed of Ca2+ influx. The sustained phase was significantly attenuated by 100 nMclomipramine and verapamil. The present findings demonstrate that clomipramine and verapamil, in their therapeutic concentrations, have a common action of inhibiting Ca2+ influx, and suggest that the calcium antagonistic effect may play an important role in clinical effects of antidepressan

ISSN:0302-282X    

DOI:10.1159/000119249

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In this study, the effects of chronic ethanol treatment on inositol 1,4,5-tris-phosphate (IP3) and inositol 1,3,4,5-tetrakisphosphate (IP4) specific binding in rat brain was investigated. In the cerebellum, chronic, but not acute, ethanol treatment caused a decrease in the number of IP3 receptors. The effect of chronic ethanol treatment on IP3 and IP3 receptor mRNA levels was also studied in order to determine the mechanisms responsible for the decrease in IP3 receptor binding. Chronic ethanol treatment did not change IP3 levels, indicating that the decrease of IP3 receptors is not caused by the alteration of IP3 levels. Also IP3 receptor mRNA levels had no change after chronic ethanol treatment. These findings suggest that the decrease in IP3 receptors in the cerebellum could be caused by either a decrease in the translation of IP3 receptor mRNA or an increase in proteolysis of IP3 receptors. In contrast, chronic ethanol treatment had no effect on the Bmax or Kd of IP4 specific binding in the cerebellum. It is speculated that a change at the level of the IP3 receptor in the cerebellum may be associated with the development of adaptation and tolerance to chronic ethanol exposure.

ISSN:0302-282X    

DOI:10.1159/000119250

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We examined the chronic effects of desipramine and mianserin on increases of intracellular Ca2+ concentration ([Ca2+]¡) induced by noradrenaline (NA), acetylcholine (ACh), or high K+ in cultured neurons of rat frontal cortex, using fluoromicroscopic analysis with Ca2+-sensitive dye fura-2. NA- and ACh-induced [Ca2+]¡ increases were abolished in the presence of 1 µM prazosin and 1 µM atropine, respectively, and partially inhibited in the absence of extracellular Ca2+. When cultures were treated with 1 µM desipramine for 5 days, the dose-dependent curves of NA- and ACh-induced (0.01–100 µM) [Ca2+]i increases were similar to those of the control cultures. Neither NA- nor ACh-induced [Ca2+]i increases were affected by desipramine exposure, even at a concentration of 10 µM. Treatment with mianserin (0.1, 1, or 10 µM) for 5 days had no effect on either NA- or ACh-induced [Ca2+]i increases. Additionally, [Ca2+]i increases induced by high K+ (12.5–50 mM) were not affected following chronic 10 µM desipramine exposure for 5 days. Thus, chronic anti-depressant exposure does not modify the [Ca2+]i increases mediated by α1-adrenoceptors, muscarinic cholinergic receptors, or voltage-sensitive Ca2+ channels. Changes in Ca2+ mobilization may not be one of the mechanisms of an

ISSN:0302-282X    

DOI:10.1159/000119251

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In order to establish possible alterations in the secretory patterns of adrenocorticotropic hormone (ACTH), cortisol and/or β-endorphin in bulimia nervosa, the circadian fluctuations of these hormones were evaluated in blood samples taken at 1-hour intervals over 24 h. Eleven bulimic women with normal body weight and 8 weight- and age-matched normal controls were tested during the follicular phase (days 6-8) of normal menstrual cycles. All women were hospitalized for bulimia or for checkup examinations and were tested 3 days after hospital admission. Both normal and bulimic women showed maximal ACTH, cortisol and β-endorphin levels at 08.00 h, with minimal ACTH and β-endorphin levels at midnight and cortisol levels at 02.00 h. The general temporal structure of all hormonal secretions coincided in the two groups. However, whereas all measured ACTH/cortisol levels were quantitatively similar in the two groups, plasma β-endorphin concentrations were significantly higher in bulimic than in control subjects at all examined time points. The enhancement in the overall 24-hour β-endorphin secretion suggests the presence of an increased opioid tonus in bulimic women, which might play a role in the pathophysiology of the eating diso

ISSN:0302-282X    

DOI:10.1159/000119252

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effect of a neuroleptic, haloperidol (HP), on nitric oxide formation catalyzed by neuronal nitric oxide synthase (n-NOS) in the porcine brain was investigated. HP inhibited n-NOS activity noncompetitively versus L-arginine as a substrate, decreasing the maximal velocity (Ki value for HP = 31 µM). HP also inhibited the CaM-dependent NADPH consumption by n-NOS (IC50 = 221 µM). These data demonstrate the possibility that HP may mediate some neuronal functions through inhibiting NO release by preventing either the electron transfer through n-NOS or the formation of the activated reduced species of oxygen necessary for the formation of citrulline. And an interaction of HP with CaM may possibly affect the consumption of NADPH and n-NOS enzyme activit

ISSN:0302-282X    

DOI:10.1159/000119253

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Anticholinergic treatment of neuroleptic extrapyramidal movement disorders (EPS) has been associated with induction of tardive dyskinesia. Also an increasing abuse of anticholinergics by schizophrenic patients is noted. Since as early as 1976, positive effects of amantadine (AMA) on neuroleptic EPS have been described, therefore a controlled study of these reports seemed worthwhile. Forty-two schizophrenic patients (of which 7 were dropouts) of three centers entered the study and were treated for EPS in a double-blind design: 18 (11 m, 7 f) with AMA and 17 (8 m, 9 f) with biperiden (BIP). Identical preparations of AMA (100 mg, tid) and BIP (2 mg, tid) were used in treatment of haloperidol-induced EPS (AMA, mean 22.4 mg haloperidol; BIP, mean 19.6 mg haloperidol). Effects of treatment and possible side effects were rated: EPS for the intensity of EPS, BPRS for quantification of psychotic symptoms, FSUCL for rating the side effects and KUSTA to document patients’ mood. Ratings were recorded on days 0, 3, 7, 14, 28 and at discontinuation, respectively. All patients were treated with haloperidol and levomepromazine (for tranquilization/sleep induction) and the respective antiparkinsonian agent for 14 days. Patient characteristics did not differ significantly in either groups. In the AMA treatment group, 2 patients dropped out for noncompliance, in the BIP group, 5 (3 no effect, 1 noncompliance, 1 agitation). All results as recorded with the different rating instruments showed a significant (p < 0.01) overall improvement, whereas no significant differences between treatment groups could be determined, notably the treatment effect of both drugs on EPS was similar. Thus, the application of AMA in cases of neuroleptic EPS seems justified and is a useful alternative to anticholinergic drugs. Certain advantageous aspects of AMA treatment of EPS with regard to the glutamate hypothesis of schizophrenia and tardive dyskinesia are discusse

ISSN:0302-282X    

DOI:10.1159/000119254

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of catecholamines and serotonin, respectively. The present study was conducted to determine the levels of 6R-BH4 in the inbred strains of rats BN and F344, and the inbred strains of mice C57BL/6J, C3H/HeJ and DBA/2J, with different genetically determined alcohol preferences. Previous studies have shown that BN and F344 rats exhibit a high and low alcohol preference, respectively; that C57BL/6J and DBA/2J mice show a high and low alcohol preference, respectively, and that C3H/HeJ mice exhibit a moderate alcohol preference. The levels of 6R-BH4 were measured in five regional brain areas of rats and in two regional brain areas of mice. There was about a 3-fold difference in 6R-BH4 levels across the rat brain areas assayed, ranging from a low level in the frontal cortex to a high level in the striatum and midbrain. Midbrain 6R-BH4 levels in F344 rats were higher than those of BN rats (p < 0.05). On the other hand, striatal 6R-BH4 levels in DBA/2J mice were higher than those of the other two strains of mice (p < 0.05). These results indicate that 6R-BH4 is distributed throughout the nigro- and mesostriatal dopaminergic nervous systems, and that brain 6R-BH4 levels may be involved in the genetic differences in alcohol-drinking behavior in animal models.

ISSN:0302-282X    

DOI:10.1159/000119255

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

In order to investigate influences of corticotropin-releasing hormone (CRH) and corticotropin fragment (adrenocorticotropic hormone, ACTH, 4–9) on auditory perception processes, 10 subjects received either a placebo (sodium chloride 0.9%), CRH (100 µg) or ACTH 4–9 (Hoe 427, 300 µg) intravenously on different days. Late auditory evoked potentials (AEP) were computed and further analyzed using the brain electric source analysis method. As expected, CRH administration was followed by a rise in plasma cortisol and ACTH concentrations, whereas the injection of the ACTH 4–9 fragment did not alter plasma cortisol concentrations. In contrast to these different hormonal responses, both CRH and ACTH 4–9 modulated AEP in a similar manner, differing in quantity rather than in quality. The changes in AEP after the administration of ACTH 4–9 were most likely induced by a direct CNS action, whereas for the CRH effects, an indirect mechanism through the release of endogenous ACTH must be

ISSN:0302-282X    

DOI:10.1159/000119256

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The cerebral basis of obsessions and compulsions has attracted increasing attention in neuropsychology and neuropsychiatry. Clinical and imaging studies have suggested frontal lobe dysfunction in some cases of obsessive-compulsive disorder and Tourette syndrome with obsessional symptoms. We compared EEG spectral measures in 20 such patients not taking medications and 12 neurologically intact unmedicated controls. EEG was recorded from 01-A1+A2, O2-A1+A2, Fz-A1+A2, F7-C3, F8-C4, T5-O1 and T6-O2. One-minute epochs of artifact-free EEG were used for compressed spectral array and calculation of time domain descriptors. We measured modal alpha frequency (MAF), maximal alpha frequency (MxAF), spectral edge frequency and spectral mobility in left and right frontal regions (MOLF and MORF). MAF and MxAF were reduced in the frontal regions in patients as compared to controls, and MOLF and MORF were both lower. No significant differences between patients and controls were found in the temporal or occipital areas. These observations support the suggestions of a physiologic basis for obsessions and compulsions, and of frontal lobe disturbance in their pathophysiology.

ISSN:0302-282X    

DOI:10.1159/000119257

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

The effects of drugs on electrocorticographic activity (ECoG) of the rat are studied in a routine screen. ECoG is recorded for 6-min periods before drug/ vehicle administration and starting at 20 and 45 min thereafter. For each period, a mean power spectrum is calculated. Drugs are tested in 25 rats according to a 5 × 5 Latin square design and effects are assessed with analysis of variance. The validity of this assessment depends on assumptions on the chosen statistical model and the distribution of the data. In this study we consider the relative and absolute baseline corrected data. The assumptions appear to be better fulfilled if together with a relative baseline correction a logarithmic transformation is applied to the data

ISSN:0302-282X    

DOI:10.1159/000119258

出版商:S. Karger AG    

年代:1996

数据来源: Karger